Pharmacokinetics and pharmacodynamics of epsilon-aminocaproic acid in horses.
Abstract: To determine the pharmacokinetics and pharmacodynamics of epsilon-aminocaproic acid (EACA), including the effects of EACA on coagulation and fibrinolysis in healthy horses. Methods: 6 adult horses. Methods: Each horse received 3.5 mg of EACA/kg/min for 20 minutes, i.v. Plasma EACA concentration was measured before (time 0), during, and after infusion. Coagulation variables and plasma alpha(2)-antiplasmin activity were evaluated at time 0 and 4 hours after infusion; viscoelastic properties of clot formation were assessed at time 0 and 0.5, 1, and 4 hours after infusion. Plasma concentration versus time data were evaluated by use of a pharmacokinetic analysis computer program. Results: Drug disposition was best described by a 2-compartment model with a rapid distribution phase, an elimination half-life of 2.3 hours, and mean residence time of 2.5 +/- 0.5 hours. Peak plasma EACA concentration was 462.9 +/- 70.1 microg/mL; after the end of the infusion, EACA concentration remained greater than the proposed therapeutic concentration (130 microg/mL) for 1 hour. Compared with findings at 0 minutes, EACA administration resulted in no significant change in plasma alpha(2)-antiplasmin activity at 1 or 4 hours after infusion. Thirty minutes after infusion, platelet function was significantly different from that at time 0 and 1 and 4 hours after infusion. The continuous rate infusion that would maintain proposed therapeutic plasma concentrations of EACA was predicted (ie, 3.5 mg/kg/min for 15 minutes, then 0.25 mg/kg/min). Conclusions: Results suggest that EACA has potential clinical use in horses for which improved clot maintenance is desired.
Publication Date: 2007-09-04 PubMed ID: 17764418DOI: 10.2460/ajvr.68.9.1016Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article investigates how epsilon-aminocaproic acid (EACA) works within horses’ bodies (pharmacokinetics) and the effects it has (pharmacodynamics), including its impact on blood clotting and fibrinolysis.
Research Methods and Objectives
- Researchers aimed to establish the pharmacokinetic and pharmacodynamic attributes of epsilon-aminocaproic acid (EACA) in horses. EACA is an agent known to impact the process of blood clotting and fibrinolysis, thus the study was designed to explore these effects.
- For the study, six adult horses were selected and each was given 3.5 mg of EACA per kg of body weight over a period of 20 minutes intravenously (i.v).
- The researchers measured the concentration of EACA in the plasma of the horses before, during, and after the infusion of the drug.
- Coagulation variables and plasma alpha(2)-antiplasmin activity was assessed at the beginning (time 0) and 4 hours after infusion. Also, the viscoelastic properties of clot formation were evaluated at specified time intervals following the infusion.
- To process the collected data, a pharmacokinetic analysis computer program was used.
Findings
- The results showed that the drug’s disposition aligns with a two-compartment model characterized by a rapid distribution phase and a drug elimination half-life of about 2.3 hours.
- The peak plasma EACA concentration was observed to be approximately 462.9 +/- 70.1 microg/mL, and this concentration remained above the proposed therapeutic concentration of 130 microg/mL for an hour after the infusion ended.
- There was no significant change in plasma alpha(2)-antiplasmin activity at 1 or 4 hours after the infusion, compared to the findings at the start.
However, 30 minutes after the infusion, a significant alteration in platelet function was observed, which was different from that at time 0 and at 1 and 4 hours post-infusion. - Based on these findings, the research predicts a continuous infusion rate that would sustain the proposed therapeutic plasma concentrations of EACA. This was estimated to be 3.5 mg/kg/min for the first 15 minutes, followed by 0.25 mg/kg/min.
Conclusion
- The results from this study suggest that EACA could potentially be applied clinically in horses where enhanced clot maintenance is desired.
Cite This Article
APA
Ross J, Dallap BL, Dolente BA, Sweeney RW.
(2007).
Pharmacokinetics and pharmacodynamics of epsilon-aminocaproic acid in horses.
Am J Vet Res, 68(9), 1016-1021.
https://doi.org/10.2460/ajvr.68.9.1016 Publication
Researcher Affiliations
- Department of Clinical Studies, New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA 19348, USA.
MeSH Terms
- Aminocaproic Acid / blood
- Aminocaproic Acid / pharmacokinetics
- Aminocaproic Acid / pharmacology
- Animals
- Antifibrinolytic Agents / blood
- Antifibrinolytic Agents / pharmacokinetics
- Antifibrinolytic Agents / pharmacology
- Area Under Curve
- Female
- Fibrinogen / metabolism
- Half-Life
- Horses / blood
- Horses / metabolism
- Infusions, Intravenous
- Partial Thromboplastin Time / veterinary
- Prothrombin Time / veterinary
- Statistics, Nonparametric
- alpha-2-Antiplasmin / metabolism
Citations
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